Aducanumab: Appropriate Use Recommendations Update.

Area of Science:

• Neurology
• Pharmacology
• Medical Guidelines

Background:

• Aducanumab is approved for mild cognitive impairment and mild dementia due to Alzheimer's disease.
• Published Appropriate Use Recommendations (AURs) have guided aducanumab's real-world application.
• Evolving clinical experience necessitates refinement of these AURs.

Purpose of the Study:

• To update the AURs for aducanumab to improve patient selection, shared decision-making, and safety monitoring.
• To provide guidance on risk mitigation for patients receiving aducanumab treatment.
• To incorporate new information from real-world use into clinical practice recommendations.

Main Methods:

• Review of evolving clinical experience and accrued data on aducanumab use.
• Emphasis on identifying predisposing medical conditions for amyloid-related imaging abnormalities (ARIA).
• Inclusion of apolipoprotein E ε4 (APOE4) genotyping recommendations and specific MRI monitoring schedules.

Main Results:

• Identification of risk factors for ARIA, including autoimmune conditions, seizures, and white matter pathology.
• Strong association between APOE4 genotype and ARIA, with a gene dose effect.
• Recommended MRI scans before the 5th, 7th, 9th, and 12th aducanumab infusions to detect ARIA.

Conclusions:

• Updated AURs aim to optimize patient selection and safety monitoring for aducanumab therapy.
• APOE genotyping is recommended to inform risk discussions and clinical vigilance for ARIA.
• Continued learning from real-world aducanumab use will guide future AUR evolution.